Enhanced biomedical potential of polyurethane/hydroxyapatite composites through chemical modification: A comprehensive study on structure, morphology, and cytocompatibility for tissue regeneration.

Polyurethane/hydroxyapatite (PU/HA) composites are well-known for various biomedical applications. This study reports a chemical approach to improve the interaction between HA and PU matrix. HA was surface-modified with 1,6-hexamethylene diisocyanate (HMDI). First, an isocyanate-modified HA (IHA) was synthesized by hydro-thermal method. Second, IHA was incorporated into a separately synthesized thermoplastic PU by a solvent casting technique. A series of PU/IHA composites was prepared by varying PU᾿s soft and hard segments. The IHA was added to PU (5 and 10 %). The FTIR spectra exhibited characteristic bands of urethane and HA, confirming the synthesis of the composites. XRD study showed the crystallite size of IHA (20 Å) with hexagonal geometry and an amorphous to semicrystalline nature of composites. SEM showed that composites displayed porous and granular morphology. The TGA thermograms of the composites revealed the thermal stability up to 400 °C. The IHA addition considerably improved hydrophilicity and degradation of the composites in simulated body fluid (SBF). MTT assay revealed improved cytocompatibility (> 80 %) of the composites. These results demonstrated an appreciable improvement in structure, morphology, hydrophilicity, degradation, and cytocompatibility of PU/IHA composites by chemical modification of HA. Hence, these composites possess remarkable potential for biomedical applications such as tissue regeneration.

Patient-reported Outcomes After Medial Meniscus Root Tear Repair Versus Other Medial Meniscus Repairs: An Exploratory Meta-analysis of Single-arm Cohorts.

INTRODUCTION: This study aimed to (1) compare patient-reported outcome measures between patients who underwent medial meniscus root tear (MMRT) repair and those who underwent other types of medial meniscus repair, and (2) identify factors associated with observed differences. METHODS: A literature search identified studies reporting PROMs-knee injury and osteoarthritis outcome score (KOOS) or visual analog scale (VAS) for pain-after repair of the medial meniscus. Studies were excluded if outcomes were not separated by tear type or reported graphically, different or no outcomes reported, no repair or repair with a sutureless method, follow-up greater than 72 months, case report, and systematic review. Patient-reported outcome measures and demographics were summarized as sample-weighted means and compared using t-tests. Mixed model linear regressions were fit predicting postoperative PROMs adjusted for tear type, preoperative PROMs, and follow-up time. F statistics of type III tests of fixed effects were compared. RESULTS: Eighteen articles were included, n = 10 received MMRT repair and n = 8 other tear repairs. Postoperative values for all KOOS scores were less for the MMRT repair group compared with the other tear repair group, VAS pain was not statistically different. Tear type was a stronger predictor for postoperative PROMs than the preoperative score and duration of follow-up for all KOOS scores, but not VAS pain. On average, the MMRT repair group had shorter follow-up, more women, older age, and greater BMI. DISCUSSION: All postoperative PROMs except for VAS pain were worse for patients who underwent MMRT repair compared with patients who underwent other types of medial meniscus repair. Tear type was a better predictor of postoperative PROMs despite intergroup differences in preoperative PROMs and duration of follow-up. Relative risk factors for MMRT compared with other types of medial meniscus tears include older age, greater BMI, and female sex.

Evaluating Nanoparticulate Vaccine Formulations for Effective Antigen Presentation and T-Cell Proliferation Using an In Vitro Overlay Assay.

Inducing T lymphocyte (T-cell) activation and proliferation with specificity against a pathogen is crucial in vaccine formulation. Assessing vaccine candidates' ability to induce T-cell proliferation helps optimize formulation for its safety, immunogenicity, and efficacy. Our in-house vaccine candidates use microparticles (MPs) and nanoparticles (NPs) to enhance antigen stability and target delivery to antigen-presenting cells (APCs), providing improved immunogenicity. Typically, vaccine formulations are screened for safety and immunostimulatory effects using in vitro methods, but extensive animal testing is often required to assess immunogenic responses. We identified the need for a rapid, intermediate screening process to select promising candidates before advancing to expensive and time-consuming in vivo evaluations. In this study, an in vitro overlay assay system was demonstrated as an effective high-throughput preclinical testing method to evaluate the immunogenic properties of early-stage vaccine formulations. The overlay assay's effectiveness in testing particulate vaccine candidates for immunogenic responses has been evaluated by optimizing the carboxyfluorescein succinimidyl ester (CFSE) T-cell proliferation assay. DCs were overlaid with T-cells, allowing vaccine-stimulated DCs to present antigens to CFSE-stained T-cells. T-cell proliferation was quantified using flow cytometry on days 0, 1, 2, 4, and 6 upon successful antigen presentation. The assay was tested with nanoparticulate vaccine formulations targeting Neisseria gonorrhoeae (CDC F62, FA19, FA1090), measles, H1N1 flu prototype, canine coronavirus, and Zika, with adjuvants including Alhydrogel® (Alum) and AddaVax™. The assay revealed robust T-cell proliferation in the vaccine treatment groups, with variations between bacterial and viral vaccine candidates. A dose-dependent study indicated immune stimulation varied with antigen dose. These findings highlight the assay's potential to differentiate and quantify effective antigen presentation, providing valuable insights for developing and optimizing vaccine formulations.

In Vitro Human Gastrointestinal Digestibility and Colonic Fermentation of Wheat Sourdough and Yeast Breads.

Bread can vary in textural and nutritional attributes based on differences in the bread making process (e.g., flour type, fermentation agent, fermentation time). Four bread recipes (BRs) made with sourdough preferments (BR1, white flour; BR2, whole grain flour) or regular yeast breads (BR3, white flour; BR4, whole grain flour) were evaluated for texture, digestibility, and their effect on the metabolic activity and composition of the gut microbiota using texture profile analysis (TPA) coupled with in vitro upper gastrointestinal (GIT) digestion and colonic fermentation (Colon-on-a-plate™ model), using fecal samples from eight healthy human donors. TPA revealed significantly higher values for hardness, fracturability, gumminess, and chewiness, and significantly lower values for springiness, cohesiveness, and resilience with whole grain versus white breads (all p < 0.001); values for springiness, cohesiveness, and resilience were significantly higher for sourdough versus yeast bread (p < 0.001). Nutrient composition and bioaccessibility were generally comparable between sourdough and yeast bread with similar flours. Following simulation of upper GIT digestion, all BRs demonstrated good digestibility of minerals, carbohydrates, and proteins. Colonic fermentation revealed changes in gut microbiota composition, significant increases in short-chain fatty acids, and a significant decrease in branched short-chain fatty acids with all BRs versus a blank. Overall, new insights into wheat bread digestibility and colonic fermentation were provided, which are important aspects to fully characterize bread nutritional profile and potential.

Pravastatin Protects Cytotrophoblasts from Hyperglycemia-Induced Preeclampsia Phenotype.

There are no effective therapies to prevent preeclampsia (PE). Pravastatin shows promise by attenuating processes associated with PE such as decreased cytotrophoblast (CTB) migration, aberrant angiogenesis, and increased oxidative stress. This study assesses the effects of pravastatin on hyperglycemia-induced CTB dysfunction. METHODS: Human CTB cells were treated with 100, 150, 200, 300, or 400 mg/dL glucose for 48 h. Some cells were pretreated with pravastatin (1 µg/mL), while others were cotreated with pravastatin and glucose. The expression of urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) mRNA, vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin (sEng) were measured. CTB migration was assayed using a CytoSelect migration assay kit. Statistical comparisons were performed using an analysis of variance with Duncan's post hoc test. RESULTS: The hyperglycemia-induced downregulation of uPA was attenuated in CTB cells pretreated with pravastatin at glucose levels > 200 mg/dL and cotreated at glucose levels > 300 mg/dL (p < 0.05). Hyperglycemia-induced decreases in VEGF and PlGF and increases in sEng and sFlt-1 were attenuated in both the pretreatment and cotreatment samples regardless of glucose dose (p < 0.05). Pravastatin attenuated hyperglycemia-induced dysfunction of CTB migration. CONCLUSIONS: Pravastatin mitigates stress signaling responses in hyperglycemic conditions, weakening processes leading to abnormal CTB migration and invasion associated with PE in pregnancy.

Emerging Trends and Innovations in the Treatment and Diagnosis of Atherosclerosis and Cardiovascular Disease: A Comprehensive Review towards Healthier Aging.

Cardiovascular diseases (CVDs) are classed as diseases of aging, which are associated with an increased prevalence of atherosclerotic lesion formation caused by such diseases and is considered as one of the leading causes of death globally, representing a severe health crisis affecting the heart and blood vessels. Atherosclerosis is described as a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease and to date, most pharmacological therapies mainly aim to control risk factors in patients with cardiovascular disease. Advances in transformative therapies and imaging diagnostics agents could shape the clinical applications of such approaches, including nanomedicine, biomaterials, immunotherapy, cell therapy, and gene therapy, which are emerging and likely to significantly impact CVD management in the coming decade. This review summarizes the current anti-atherosclerotic therapies' major milestones, strengths, and limitations. It provides an overview of the recent discoveries and emerging technologies in nanomedicine, cell therapy, and gene and immune therapeutics that can revolutionize CVD clinical practice by steering it toward precision medicine. CVD-related clinical trials and promising pre-clinical strategies that would significantly impact patients with CVD are discussed. Here, we review these recent advances, highlighting key clinical opportunities in the rapidly emerging field of CVD medicine.

Analysis of IDH and EGFR as biomarkers in glioblastoma multiforme: A case-control study.

Background: Glioblastoma multiforme (GBM) is a very aggressive primary central nervous system (CNS) tumor with limited therapeutic options and poor prognosis. This study aimed to analyze the association between single nucleotide polymorphisms (SNPs), including IDH1 rs121913500C > T, IDH2 rs11540478G > A, and EGFR rs1468727C > T, and their association on the risk and overall survival of GBM patients in Jordan. Methods: Using a case-control study design involving 63 GBM patients and 226 healthy controls was conducted at King Abdullah University Hospital in Jordan. DNA extraction was performed using formalin-fixed and paraffin-embedded tissue for GBM samples and blood samples for controls. SNPs analysis was performed using the Sequenom iPLEX assay sequencing technique. Survival outcomes were assessed using Cox models and hazard ratios (HR), and single-cell RNA (scRNA) analysis was performed from GSE70630. Results: The study showed a significant association between genotype frequency in GBM cases and controls for specific SNPs, including IDH1 rs121913500C > T, and EGFR rs1468727C > T. The G/G genotype of rs11540478 (IDH2) was associated with better prognostic outcomes in GBM patients. The scRNA analysis demonstrated the differential expression of IDH1, IDH2, and EGFR in GBM, with enrichment in central carbon metabolism in cancer. Conclusion: Our findings suggest that SNPs, particularly in IDH1 and IDH2 genes and EGFR, may serve as diagnostic and prognostic biomarkers for GBM. While the study underscores the clinical relevance of these genetic variants, further investigations with larger and more diverse populations are essential to validate and extend these associations.

Predictive factors for readmission after bariatric surgery: Experience of an obesity center.

Avoidable readmissions after bariatric surgery are a major burden on the healthcare systems. Rates of readmission after bariatric surgery have ranged from 1% up to 20%, but the factors that predict readmission have not been well studied. The objective of this study was to determine readmission rates following bariatric surgery and identify factors that contribute to early (within 90 days of surgery) and late readmission. A retrospective cohort study of 736 patients undergoing either Laparoscopic Sleeve Gastrectomy or Laparoscopic Roux-en-Y Gastric Bypass in Jordan University Hospital from 2016 to 2019. Demographic characteristics, co-morbidities, and readmissions were extracted from their medical records and analyzed. Multivariable logistic regression analysis was performed to determine which factors predict readmission. A total of 736 patients had bariatric surgery (Laparoscopic Sleeve Gastrectomy 89% vs Laparoscopic Roux-en-Y Gastric Bypass 11%) during the study period. Thirty-day readmission rate was 6.62% and an overall readmission rate of 23.23%. Common reasons for early readmission (within 90 days of surgery) were nausea, vomiting, and dehydration. Late readmissions were mainly caused by gallbladder stones. Three risk factors were identified that independently predicted readmission: the type of procedure being performed (P-value = .003, odds ratio [OR] 2.14, 95% confidence interval [CI] 1.32-3.49), depression (P-value = .028, OR 6.49, 95% CI 1.18-52.9) and preoperative body mass index (P-value = .011, OR 1.03, 95% CI 1.01-1.05). Several factors were identified that cause patients to represent and subsequently admitted into hospitals. Early readmission was usually due to nausea, vomiting, and dehydration, whereas late admissions were mostly due to biliary complications. Preoperative body mass index and depression were independent risk factors for readmission.

Qualitative analysis of the Supraspinatus muscle fatty infiltration on MRI - Correlation of the Tangent sign with Goutallier grade at the Y view and Medial Scapular border in large retracted rotator cuff tears.

BACKGROUND: Surgically repairing rotator cuff tears with a higher extent of fatty infiltration is controversial. Current evidence supports performing rotator cuff repair in patients exhibiting Goutallier stage 3-4 fatty infiltration. However, the presence of retraction complicates accurate assessment using the Goutallier Classification, particularly on the lateral Y-view. A shift towards classifying fatty infiltration in more medial regions may enhance the precision of tissue quality quantification. The objective of this study was to analyze the uniformity of fatty infiltration within the entire supraspinatus muscle using the Goutallier Classification across three scapular Y-view sections and to examine the association between Goutallier grade, tangent sign, and modified Patte stage. METHODS: A retrospective evaluation was conducted on preoperative magnetic resonance imaging (MRI) scans from a consecutive series of 97 patients who had previously undergone arthroscopic rotator cuff repairs. Three supraspinatus sections on the MRI sagittal plane were identified: the lateral Y-view (section one), a medial section at the suprascapular notch anatomical landmark (section two), and a section 3 cm medial from the suprascapular notch Medial Scapular Body (section three). Goutallier grade, tangent sign, and modified Patte stage were used to evaluate fatty infiltration, muscle atrophy, and tendon retraction, respectively. RESULTS: Section one had the highest Goutallier grade, while section three had the lowest. Intra-observer rest retest reliability analysis showed excellent consistency in all sections with section one (ICC=0.920, 95% CI), section two (ICC=0.917, 95% CI), and section three (ICC=0.923, 95% CI) for Goutallier grade. Inter-observer reliability analysis also revealed excellent consistency in sections one (ICC=0.951, 95% CI), section two (ICC=0.949, 95% CI), and section three (ICC=0.922, 95% CI) for Goutallier grade. A strong correlation was observed between Goutallier grade and modified Patte stage (τb=0.43-0.56, p=0.001), and between Goutallier grade and tangent sign (τb=0.43-0.54, p=0.001) across all sections. CONCLUSION: The severity of fatty infiltration within the supraspinatus muscle belly is inconsistent, with the lateral portion being the most severe and the medial portion the least severe. Goutallier grade demonstrates a strong correlation with tangent sign and modified Patte stage. This suggests that tendon retraction results in a potential overestimation in the amount of fatty infiltration defining some tears unjustly irreparable when measuring at the traditionally described lateral Y-view position compared with 3cm medial.

A Rare Case of Membranous Nephropathy Complicated by Chylothorax.

Background: Chylothorax can be classified into traumatic and nontraumatic based on the etiology. Nephrotic syndrome is a very rare cause of nontraumatic chylothorax in adults. Case presentation: A 66-year-old woman with membranous nephropathy who was non-compliant with her management, presented with dyspnea, and was found to have a large right sided chylothorax. Her chylothorax was secondary to membranous nephropathy after excluding other causes, which has been rarely reported in literature. Conclusion: This case highlights the possibility of nephrotic syndrome causing chylothorax, especially in patients with undiagnosed nephrotic syndrome or patients non-compliant with their management. When evaluating a patient with chylothorax, providers should consider nephrotic syndrome in the differential diagnosis. LEARNING POINTS: Chylothorax can be secondary to nephrotic syndrome which has been rarely reported in literature.Providers should be aware of nephrotic syndrome as a cause of chylothorax especially in patients with undiagnosed nephrotic syndrome or non-compliance with their management.Treatment of underlying cause is usually sufficient for spontaneous resolution of chylothorax with or without pleural fluid evacuation.